Variant 12-50437774-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000398473.7(LARP4):c.575T>C(p.Val192Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LARP4
ENST00000398473.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Variant links:

Genes affected

LARP4 (HGNC:24320): (La ribonucleoprotein 4) Enables mRNA 3'-UTR binding activity and poly(A) binding activity. Involved in cytoskeleton organization; positive regulation of translation; and regulation of cell morphogenesis. Located in cytosol. Colocalizes with cytoplasmic stress granule; cytosolic small ribosomal subunit; and polysome. [provided by Alliance of Genome Resources, Apr 2022]

LARP4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP4	NM_052879.5 linkuse as main transcript	c.575T>C	p.Val192Ala	missense_variant	6/16	ENST00000398473.7	NP_443111.4	Q71RC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARP4	ENST00000398473.7 linkuse as main transcript	c.575T>C	p.Val192Ala	missense_variant	6/16	1	NM_052879.5	ENSP00000381490.2		Q71RC2-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460034

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726412

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2023

The c.575T>C (p.V192A) alteration is located in exon 6 (coding exon 6) of the LARP4 gene. This alteration results from a T to C substitution at nucleotide position 575, causing the valine (V) at amino acid position 192 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

.;.;T;D;.;.;.;.;.;.;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.74

D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.47

MutationAssessor

Pathogenic

3.4

M;.;.;M;.;M;.;.;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.7

D;D;D;D;.;D;.;D;D;D;D

REVEL

Pathogenic

0.75

Sift

Uncertain

0.0010

D;D;D;D;.;D;.;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.89, 0.94, 0.99

.;P;.;P;.;.;.;D;.;.;.

Vest4

0.89

MutPred

0.50

Loss of methylation at K191 (P = 0.0467);.;.;Loss of methylation at K191 (P = 0.0467);.;Loss of methylation at K191 (P = 0.0467);.;.;.;Loss of methylation at K191 (P = 0.0467);.;

MVP

0.70

MPC

0.83

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over